Abstract
Our understanding of the pathogenesis of uremic pruritus (also known as CKD-associated pruritus [CKD-aP]) remains elusive. Although multiple discrete changes in the immunochemical milieu of the skin of patients with CKD-aP have been described, a coherent theory of mechanism is absent. This article proposes a theoretical model of mechanism. It concentrates on the initiation phase of CKD-aP and its three parts: ( 1 ) genesis, triggered by first precipitants; ( 2 ) cascade of cytokine release that follows and the cross-talking of multiple skin cells with each other and afferent nerve fibers; and ( 3 ) enhancement. The limitation of the model will be described and ideas for future research proposed. Implications for management shall be examined.